In Korea, pulmonary surfactant (PS) replacement therapy in respiratory distress syndrome (RDS) was started in 1991 since when Surfacten® was imported from Japan. At the present time, Surfacten®, Newfactan®, Curosurf®, and Infasurf® are available in Korea. The governmental health insurance covers the expense for multiple dose treatment since 2002 and the early prophylactic treatment (BW: <1,250 g or GP: <30 wks) since 2011. We undertook a multi-institutional collective study to evaluate the outcomes of PS over past 20 years in Korea (Period-I; 1990/91, P-II; 1996, P-III; 2002, and P-IV; 2007, P-V; 2010). There were 60 RDS neonates with PS treatment in P-I (16 hospitals), 1,179 in P-II (64), 1,595 in P-III (62), 1,921 in P-IV (57), and 3,160 in P-V (72). Decreased mortality rate, defined as the percentage of neonates who died within 28 days of birth, was seen between periods, P-V vs P-I, II, III, and IV (mortality rate: 10.1% vs. 40.0%, 30.0%, 18.7%, and 14.3%). We conclude that PS therapy contributed to improve remarkable outcome in RDS neonates over the last 20 years in Korea. However, more efforts should be made to optimize PS therapy for better outcome. Multiple PS doses for relapse and poor response, early prophylactic use, and better supportive care for pre-term infants are mandatory.